A lower birth weight percentile is associated with central corneal thickness thinning: Results from the Gutenberg Prematurity Eye Study (GPES)

Purpose: Prematurity, prenatal growth restriction, and retinopathy of prematurity (ROP) are associated with altered ocular geometry, such as a steeper corneal shape in childhood, but it is unclear whether perinatal history affects corneal thickness development, so this study investigated whether corneal thickness in adulthood is affected by perinatal history. Marterials and Methods: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. The corneal thickness was measured by Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany), and the relationship between perinatal parameters respective birth weight percentile and corneal thickness at different locations was assessed using uni- and multivariable linear regression models. Covariates included age, sex, mean corneal radius, white-to-white distance, gestational age, birth weight percentile, ROP occurrence, and treatment. The main outcome measures were corneal thickness at the apex, the pupil center, and the corneal periphery. Results: The corneal thickness was measured in 390 participants (754 eyes, mean age 29.7+/-8.7 years, 224 females). In multivariable analyses, a lower birth weight percentile was associated with a lower corneal thickness at the apex (B = 0.20, p = 0.003) and the pupil (B = 0.19, p = 0.007). These effects diminished towards the corneal periphery and were not observed beyond the 4-mm diameter circle around the thinnest corneal position. Neither gestational age, ROP occurrence, or ROP treatment affected the corneal thickness. Conclusion: A lower birth weight percentile in subjects born preterm as a proxy for restricted fetal growth is associated with corneal thickness thinning in adults aged 18 to 52 years, indicating that corneal thickness development, particularly in the corneal center, may originate in the fetal stage. (AU)

On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

BACKGROUND: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. METHODS: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. RESULTS: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). CONCLUSION: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

A lower birth weight percentile is associated with central corneal thickness thinning: Results from the Gutenberg Prematurity Eye Study (GPES).

PURPOSE: Prematurity, prenatal growth restriction, and retinopathy of prematurity (ROP) are associated with altered ocular geometry, such as a steeper corneal shape in childhood, but it is unclear whether perinatal history affects corneal thickness development, so this study investigated whether corneal thickness in adulthood is affected by perinatal history. MARTERIALS AND METHODS: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. The corneal thickness was measured by Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany), and the relationship between perinatal parameters respective birth weight percentile and corneal thickness at different locations was assessed using uni- and multivariable linear regression models. Covariates included age, sex, mean corneal radius, white-to-white distance, gestational age, birth weight percentile, ROP occurrence, and treatment. The main outcome measures were corneal thickness at the apex, the pupil center, and the corneal periphery. RESULTS: The corneal thickness was measured in 390 participants (754 eyes, mean age 29.7+/-8.7 years, 224 females). In multivariable analyses, a lower birth weight percentile was associated with a lower corneal thickness at the apex (B = 0.20, p = 0.003) and the pupil (B = 0.19, p = 0.007). These effects diminished towards the corneal periphery and were not observed beyond the 4-mm diameter circle around the thinnest corneal position. Neither gestational age, ROP occurrence, or ROP treatment affected the corneal thickness. CONCLUSION: A lower birth weight percentile in subjects born preterm as a proxy for restricted fetal growth is associated with corneal thickness thinning in adults aged 18 to 52 years, indicating that corneal thickness development, particularly in the corneal center, may originate in the fetal stage.

The role of preterm birth, retinopathy of prematurity and perinatal factors on corneal aberrations in adulthood: Results from the Gutenberg prematurity eye study.

INTRODUCTION: Prematurity and retinopathy of prematurity (ROP) are associated with altered corneal shape and reduced visual acuity in childhood, but their long-term effects on corneal shape in later life are still unclear. This study evaluated whether prematurity and related perinatal factors are associated with corneal aberrations in adulthood. METHODS: The Gutenberg Prematurity Eye Study (GPES) is a cohort study using Scheimpflug imaging of the cornea. Associations were assessed between corneal Zernike aberrations and gestational age (GA), birth weight (BW), BW percentile, ROP occurrence, ROP treatment and other perinatal factors using univariate and multivariable linear regression analyses. RESULTS: This study involved 444 eyes of 256 individuals born preterm (aged 28.1 ± 8.4 years, 146 females) and 231 eyes of 132 individuals born full-term (aged 29.8 ± 8.9 years, 77 females). Multivariable analyses revealed an association between corneal higher-order aberrations and lower birth weight percentile (B = -0.001, p < 0.001) as well as ROP treatment (B = 0.120, p = 0.03). Corneal lower-order aberrations were also associated with lower birth weight percentile (B = -0.004; p = 0.001) and ROP treatment (B = 0.838, p = 0.01) but not with ROP occurrence. Increased corneal aberrations were correlated with lower visual acuity and the spherical equivalent refractive error. CONCLUSIONS: Perinatal factors, particularly low birth weight percentile and ROP treatment lead to a more irregular corneal shape in adulthood, thereby reducing optical image quality and potentially contributing to reduced visual acuity and altered refractive error.

Dry Eye Parameters and Lid Geometry in Adults Born Extremely, Very, and Moderately Preterm with and without ROP: Results from the Gutenberg Prematurity Eye Study.

Background/Aims: This study aimed to analyze the effects of perinatal history on tear film properties and lid geometry in adults born preterm. Methods: The Gutenberg Prematurity Eye Study (GPES) is a German prospective examination of adults born preterm and term aged 18 to 52 years with Keratograph® 5M and Schirmer test I. Main outcome measures were first non-invasive tear film break-up time (F-NITBUT), bulbar redness (BR), Schirmer test, and nasal palpebral angle measurement. The associations with gestational age (GA), birth weight (BW), and BW percentile, retinopathy of prematurity (ROP), ROP treatment, and other perinatal factors were evaluated using regression analyses. Results: 489 eyes of 255 preterm and 277 eyes of 139 full-term individuals (aged 28.6 +/− 8.8 years, 220 females) were included. Of these, 33 participants (56 eyes) had a history of spontaneously regressed ROP and 9 participants (16 eyes) had a history of ROP treatment. After adjustment for age and sex, lower F-NITBUT (<20 s) was associated with ROP treatment (OR = 4.42; p = 0.025). Lower GA correlated with increased bulbar redness (B = −0.02; p = 0.011) and increased length of wetting in the Schirmer test (B = −0.69; p = 0.003). Furthermore, low GA was associated with narrowing of the nasal palpebral angle (B = 0.22; p = 0.011) adjusted for age and sex, but not when considering ROP in the multivariable model. Conclusion: Our analyses indicate that perinatal history affects ocular surface properties, tear production and lid geometry in adults born term and preterm. This might indicate that affected persons have a predisposition to diseases of the corneal surface such as the dry eye disease.

[Alterations of the anterior segment of the eye caused by exposure to UV radiation]. / UV-strahlenexpositionsbedingte Veränderungen am vorderen Augenabschnitt.

BACKGROUND: By identifying diseases of the anterior segment of the eye associated with exposure to UV light, recommendations for action can be derived. AIM: After reading this review, the reader should be familiar with UV light-associated diseases of the anterior segment of the eye. METHOD: Using a selective literature search, UV light-associated diseases of the anterior segment of the eye were identified and protective mechanisms are described. RESULTS: The UV light-associated lesions of the anterior segment of the eye include basal cell and squamous cell carcinomas, malignant melanoma of the eyelids and conjunctiva, pterygium, keratoconjunctivitis photoelectrica and climatic droplet keratopathy as well as cortical cataract. CONCLUSION: Eyeglasses for filtering UV light, sunglasses and special safety glasses, such as welding helmets and wearing headgear protect against UV light exposure to the anterior segment of the eye and the associated diseases.

Prevalence of corneal arcus and associated factors in a German population-Results from the Gutenberg Health Study.

PURPOSE: We aimed to determine the prevalence of corneal arcus and to identify associated factors in the general population of Germany. METHODS: The Gutenberg Health Study (GHS) is a population-based cohort study in Germany, which includes an ophthalmological assessment. Refraction, distance-corrected visual acuity, non-contact tonometry and anterior segment imaging were performed for the five-year follow-up examination. Anterior segment photographs were graded for the presence of corneal arcus. Prevalence estimates were computed, and multivariable logistic regression analysis was applied to determine associated factors for corneal arcus including sex, age, spherical equivalent, central corneal thickness, intraocular pressure (IOP), socio-economic status, smoking, BMI, systolic and diastolic arterial blood pressure, HbA1c, HDL-C, LDL-C, triglyceride, and lipid modifying agents. RESULTS: A total of 9,850 right and 9,745 left eyes of 9,858 subjects (59.2±10.8 years), 49.0% females were included in this cross-sectional analysis. 21.1% of men (95%-CI: 20.0%- 22.3%) had a corneal arcus in at least one eye, and 16.9% (95%-CI: 15.9%- 18.0%) of women. In multivariable analyses, the presence of corneal arcus was associated with male gender (OR = 0.54 for female, p<0.0001), higher age (OR = 2.54 per decade, p<0.0001), smoking (OR = 1.59, p<0.0001), hyperopia (OR = 1.05 per diopter, p<0.0001), thinner cornea (OR = 0.994 per µm, p<0.0001), higher IOP (OR = 1.02, p = 0.039), higher HDL-C-level (OR = 2.13, p<0.0001), higher LDL-C-level (OR = 1.21, p<0.0001), and intake of lipid modifying agents (OR = 1.26, p = 0.0001). Arcus was not associated with socio-economic status, BMI, arterial blood pressure, and HbA1c. CONCLUSIONS: Corneal arcus is a frequent alteration of the cornea in Germany and is associated with ocular parameters and systemic parameters of dyslipidemia.

Aggregated neutrophil extracellular traps occlude Meibomian glands during ocular surface inflammation.

PURPOSE: Obstructive Meibomian gland dysfunction (MGD) is one of the leading causes of evaporative dry eye disease. Meibomian glands at the eyelid secrete lipids that prevent evaporation of the aqueous tear film. The pathogenesis of obstructive MGD is incompletely understood to date. Herein, we aim to investigate the pathogenesis of obstructive MGD using murine and human samples with various forms of ocular surface inflammation. METHOD: The presence of Neutrophil extracellular Traps (NETs) was detected with immunofluorescence analysis of ocular surface discharge and biopsy samples from patients with blepharitis. Tear fluid from patients with MGD and blepharitis were evaluated for the presence of inflammatory mediators using bead based immunoassay. Murine model of allergic eye disease (AED) was performed to investigate the role of NETs in MG occlusion. RESULTS: we show that the ocular discharge from patients with blepharitis contains aggregated neutrophil extracellular traps (aggNETs). Furthermore, the ducts of human Meibomian glands affected by blepharitis were largely congested by aggNETs. Tear fluid from patients with MGD showed elevated neutrophil chemoattractants (C5a, IL6, IL8 and IL18). C5a and IL8 correlated with the degree of deficiency of tear fluid. In the murine model of allergic eye disease (AED), aggNETs accumulated in the MG leading to occlusion of their ducts and the retrograde pent-up of the fluid followed by acinar atrophy. Constraining aggNET formation by genetic or pharmacological inhibition of peptidyl arginine deiminase type 4 (PADI4) effectively reduced MG damage. CONCLUSION: We conclude that aggNETs occlude MG causing MGD after ocular surface inflammation.

Ocular Phenotype of Relaxin Gene Knockout (Rln-/-) Mice.

Purpose: To test if relaxin deficiency affects ocular structure and function we investigated expression of relaxin (Rln) and RXFP receptors (Rxfp1, Rxfp2), and compared ocular phenotypes in relaxin gene knockout (Rln-/- ) and wild type (Rln+/+ ) mice. Materials and Methods: Rln, Rxfp1 and Rxfp2 mRNA expression was detected in ocular tissues of Rln+/+ mice using RT-PCR. The eyes of 11 Rln-/- and 5 Rln+/+ male mice were investigated. Corneal and retinal thickness was assessed using optical coherence tomography. Intraocular pressure was measured using a rebound tonometer. Retinal, choroidal and sclera morphology and thickness were evaluated histologically. Eyes were collected and fixed for immunofluorescence staining or used for RNA extraction to evaluate mRNA expression using real-time PCR. Results: Rln mRNA was expressed only in the retina, whereas Rxfp1 transcripts were detected in the retina, cornea and sclera/choroid. Rxfp2 was only present in the cornea. None of these genes were expressed in the lacrimal gland, eyelid or lens. Intraocular pressure was higher and central cornea of Rln-/- mice was significantly thicker and had significantly larger endothelial cells and a lower endothelial cell density than Rln+/+ mice. Immunohistochemistry demonstrated no significant difference in AQP3 and AQP5 staining in the cornea or other regions between wildtype and Rln-/- mice. mRNA expression of Aqp4 was significantly higher in Rln-/- than in Rln+/+ corneas, whereas Col1a2, Mmp9, Timp1 and Timp2 were significantly decreased. Expression of Aqp1, Aqp4, Aqp5, Vim and Tjp1 was significantly decreased in Rln-/- compared to Rln+/+ uvea. No significant differences in these genes were detected in the retina. Retinal, choroidal and scleral thicknesses were not different and morphology appeared normal. Conclusion: The findings indicate that loss of Rln affects expression of several genes in the uvea and cornea and results in thicker corneas with altered endothelial cells. Many of the gene changes suggest alterations in extracellular matrix and fluid transport between cells.